期刊
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
卷 49, 期 8, 页码 2693-2704出版社
SPRINGER
DOI: 10.1007/s00259-022-05743-7
关键词
Radioligand therapy; Prostate cancer; Prostate-specific membrane antigen (PSMA); Self-triggered probe; Caspase-3
资金
- National Natural Science Foundation of China [92059101, 21877004, 81873907, 81920108020]
- National Key R&D Program of China [2018YFE0205300, 2018YFC1313300]
- Beijing Natural Science Foundation [JQ19026]
- Clinical Medicine Plus X-Young Scholars Project of Peking University [PKU2020LCXQ029]
- Fundamental Research Funds for the Central Universities [BMU2021RCZX018, PKU2019LCXQ023]
- National Research Foundation of Korea [2019R1A6A1A03013807, 2020R1A2C2005919]
- National Research Foundation of Korea [2020R1A2C2005919] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is a promising treatment option for mCRPC. A self-triggered probe 2 has been developed for fluorescence imaging of RLT-induced apoptosis by targeting the colocalization of PSMA and caspase-3.
Purpose Radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) is emerging as an effective treatment option for metastatic castration-resistant prostate cancer (mCRPC). An imaging-based method to quantify early treatment responses can help to understand and optimize RLT. Methods We developed a self-triggered probe 2 targeting the colocalization of PSMA and caspase-3 for fluorescence imaging of RLT-induced apoptosis. Results The probe binds to PSMA potently with a K-i of 4.12 nM, and its fluorescence can be effectively switched on by caspase-3 with a K-m of 67.62 mu M. Cellular and in vivo studies demonstrated its specificity for imaging radiation-induced caspase-3 upregulation in prostate cancer. To identify the detection limit of our method, we showed that probe 2 could achieve 1.79 times fluorescence enhancement in response to Lu-177-RLT in a medium PSMA-expressing 22Rv1 xenograft model. Conclusion Probe 2 can potently bind to PSMA, and the fluorescence signal can be sensitively switched on by caspase-3 both in vitro and in vivo. This method may provide an effective tool to investigate and optimize PSMA-RLT.
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